Prednisone treatment inhibits the differentiation of B lymphocytes into plasma cells in MRL/MpSlac-lpr mice
Prednisone treatment inhibits the differentiation of B lymphocytes into plasma cells in MRL/MpSlac-lpr mice
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泼尼松治疗抑制 MRL/MpSlac-lpr 小鼠 B 淋巴细胞分化为浆细胞
DOI：
10.1038/aps.2015.76
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发表时间：
2015-11-01
影响因子：
8.2
通讯作者：
Wei, Wei
中科院分区：
文献类型：
--
作者：
Yan, Shang-xue;Deng, Xiao-mei;Wei, Wei
目的：大量证据表明，B淋巴细胞向浆细胞的分化在狼疮的发病过程中起重要作用。在这项研究中，我们研究了强尼松（一种经典的自身免疫性疾病治疗药物）如何调节MRL/MpSlac-lpr小鼠的浆细胞分化。方法：用强的松治疗MRL/lpr小鼠（2.5或5 mg.kg(-1)）。D (-1), ig)治疗13周，监测尿蛋白水平和生存时间。小鼠安乐死后，采集血液、脾脏和胸腺。采用ELISA试剂盒检测血清抗dsdna抗体、抗核抗体、IL-21、IL-10水平。用流式细胞术定量测定脾脏B淋巴细胞亚群和T淋巴细胞亚群。采用qPCR和Western blot检测转录因子Blimp-1和Bcl-6的表达。结果：泼尼松剂量依赖性地减轻MRL/lpr小鼠狼疮症状，降低蛋白尿水平，延长生存时间，降低血清抗核抗体水平，降低脾脏和胸腺指数。强的松治疗还显著降低了浆细胞和浆细胞前体的升高百分比，降低了活化T细胞的百分比，增加了CD4(+)CD62L（+）细胞的频率，表明抗核抗体的降低和狼疮症状的改善与浆细胞的减少有关。此外，强的松治疗降低了MRL/lpr小鼠血清IL-21和IL-10水平，降低了脾Blimp-1和Bcl-6（浆细胞分化的两个关键调节因子）的表达。结论：强尼松治疗抑制MRL/lpr小鼠B淋巴细胞向浆细胞分化，可能与抑制IL-21分泌、恢复Blimp-1与Bcl-6平衡有关。
Aim: A number of evidence shows that the differentiation of B lymphocytes into plasma cells plays an important role in lupus pathogenesis. In this study we investigated how prednisone, a classical therapeutic drug for autoimmune diseases, regulated plasma cell differentiation in MRL/MpSlac-lpr mice.Methods: MRL/lpr mice were treated with prednisone (2.5 or 5 mg.kg(-1).d(-1), ig) for 13 weeks, and the proteinuria levels and survival times were monitored. After the mice were euthanized, blood sample, spleen and thymus were collected. The serum levels of anti-dsDNA antibody, anti-nuclear antibody, IL-21, and IL-10 were detected using ELISA kits. Subsets of splenic B and T lymphocytes were quantified with flow cytometry. Transcription factor Blimp-1 and Bcl-6 expression was determined using qPCR and Western blot.Results: Prednisone treatment dose-dependently attenuated the lupus symptoms in MRL/lpr mice with decreased proteinuria levels, prolonged survival times, decreased serum anti-nuclear antibody levels, and reduced spleen and thymus indices. Prednisone treatment also significantly decreased the elevated percentages of plasma cells and plasma cell precursors, decreased the percentages of activated T cells, and increased the frequency of CD4(+)CD62L(+) cells, demonstrated that decreased anti-nuclear antibodies and improvements in lupus symptoms were associated with decreased plasma cells. Furthermore, prednisone treatment decreased serum IL-21 and IL-10 levels and reduced the expression of splenic Blimp-1 and Bcl-6 (two key regulatory factors for plasma cell differentiation) in MRL/lpr mice.Conclusion: Prednisone treatment restricts B lymphocyte differentiation into plasma cells in MRL/lpr mice, which may be correlated with the inhibition of IL-21 production and the restoration of the balance between Blimp-1 and Bcl-6.